Production of a novel viral suppressive activity associated with resistance to infection among female sex workers exposed to HIV type 1

To investigate mechanisms of natural resistance to human immunodeficiency v irus type 1 (HIV-1), we obtained blood samples from eight women who remaine d HIV-1 negative after >3 years of high-risk sex work in Chiang Rai, Thaila nd. CD4(+) T lymphocytes from these highly exposed, persistently seronegati ve (HEPS) women were readily infectable in vitro with HIV-1 subtypes B and E, Autologous CD8(+) cell suppression of both HIV-1 subtypes was evident in HEPS infection cultures, but to an extent also observed in cultures from n on-HIV-exposed individuals, Furthermore, production of beta -chemokines was not enhanced in HEPS cultures. However, HEPS cultures displayed significan tly enhanced production of a soluble activity that suppressed postintegrate d HIV-1 replication. This activity was the unique product of CD4(+) T cell and monocyte cocultures, Therefore, although HEPS individuals are apparentl y susceptible to infection, the production of a postintegrated HIV-1 suppre ssive activity during monocyte-T cell interactions might protect against th e establishment of infection by limiting viral dissemination.